Module 3: Breast: Normal, Inflammations, FCC, fibroadenoma, Phylloides, Intraductal pap

Question 1

Lets begin with the basic histology of the breast. What are the three basic structures seen?

Answer 1

1. Fat Cells
2. Stroma
3. Terminal Duct Lobular Unit (TDLU)
   - -this is the functional unit of the breast lined by double layer of cells: outer myoepithelial cells (closer to the intralobular stoma) and inner cuboidal epithelial cells (facing the lumen)

Question 2

What are the two types of stroma?

Answer 2

Intralobular: between ducts but within lobule

Interlobular stroma: between the lobules

Question 3

What is the pathway that breast milk travels?

Answer 3

Terminal Duct Lobular Unit —- lactiferous Duct — Lactiferous Sinus — Nipple

Question 4

Describe the histology slides seen in younger vs older females?

Answer 4

Younger: many TDLU make up a lobule

Older females: more fat cells than stroma and hence why breasts get saggy with age

Question 5

Clinically explain cancer and mammograms

Answer 5

Fat (radiolucent) is black and stroma (radiopaque) is white on a mammogram

• -and cancer is white due to dystrophic calcification
• -therefore in an older person easy to see cancer since in older persons the breast is mostly fat (black)
• -In a younger person breast cancer is hard to see because most of the breast is stroma (White)

Question 6

Describe the histology seen in the breast of a pregnant women.

Answer 6

Proliferation/hyperplasia of lobules under the influence of estrogen in pregnancy
–physiological adenosis of the acini (functional unit)

Question 7

Which cells make milk and which ones squeeze the milk out?

Answer 7

Inner cuboidal epithelial cells make milk

Outer myoepithelial cells contract to squeeze milk from lumen — lactiferous duct — lactiferous sinus – nipple

Question 8

Which epithelial cells are considered the gatekeepers of the stroma?

Answer 8

Outer myoepithelial cells – lost in carcinoma

Question 9

Moving onto the next change in the breast tissue is Fibrocystic change. What is the origin, etiology and pathogenesis for this change?

Answer 9

Origin: TDLU
Etiology: Unopposed estrogen
—women of reproductive age
Pathogenesis: exaggerated response of BOTH breasts to estrogen

Question 10

What is the presentation for Fibrocystic changes to the breast?

Answer 10

Women of reproductive age present with bilateral cyclical mastalgia (pain during the menstrual cycle – which points to the estrogen pathogenesis)

Question 11

What does a physician place in their report if they feel fibrocystic change?

Answer 11

Lumpy Bumpy Breast

–breast is also tender

Question 12

What are two types of Fibrocystic change?

Answer 12

1. Simple/non-proliferative

2. Proliferative

Question 13

First lets start with the Simple/Non-proliferative FCC. What are some features seen on histology?

Answer 13

Image 2a:
–Abnormally distended or dilated ducts
*each of these ducts maintains a double layer of cells (inner cuboidal and outer myoepithelial)
–Apocrine metaplasia (seen in proliferative as well) (start to look like sweat glands)
*very eosinophilic cytoplasm and benign finding
NO MALIGNANT POTENTIAL

Question 14

Now for proliferative, what are some features?

Answer 14

Image 2b:

• -Epithelial hyperplasia leads to increased malignant potential
• Inner cuboidal cells (respond to estrogen) — multilayering

Question 15

What are the three types of Proliferative FCC?

Answer 15

Ductal Proliferative FCC
Sclerosing Adenosis (hyperplasia of glands) Fibrosis (desmoplasia): w.o atypica
Lobular Proliferative FCC

Question 16

First lets start with sclerosing adenosis fibrosis, what are some features?

Answer 16

1. Mimics breast cancer the most (Clinically and histologically)
2. Many terminal duct lobular units
3. Very eosinophilic cytoplasm
4. Low chance of malignant transformation because ducts are still lined by normal epithelium.
   - -single layer of inner cuboidal and outer myoepithelial
5. Fibrosis of intralobular stroma

Question 17

Next lets move on to ductal proliferation, what are some features?

Answer 17

1. Proliferation of inner cuboidal layers
   –multiple layers of inner cuboidal
   –still single layer of myoepithelial
2. Undergoes atypia
   ** becomes atypical ductal proliferative FCC also called Ductal Carcinoma in Situ that has a high chance of malignant transformation: undergoes dysplasia
3. Can becomes invasive ductal adenocarcinoma
   –destruction of outer myoepithelial layer
   and therefore allows invasion

Question 18

Finally the last type of fibrocystic change is Lobular Proliferative FCC. What are some features?

Answer 18

1. All ducts in a lobule are proliferative (entire lobule affected)
2. Undergoes atypica
   - -highest chance of malignant transformation, called LCIS: lobular carcinoma in situ
3. Finally can become invasive carcinoma
   - -loss of outer myoepithelium

Question 19

List in order the greatest to the least chance of FCC becoming malignant

Answer 19

Atypical Lobular — Atypical Ductal —- Lobular –Ductal —- Sclerosing Adenosis

Question 20

On trans-illumination of a patient with FCC, what do you see?

Answer 20

Blue-doomed cysts

Question 21

Patients with FCC can get what in the uterus?

Answer 21

Endometrial hyperplasia and this can lead to endometrial carcinoma
Also polycystic ovarian syndrome/ovarian tumor
–possible source of elevated estrogen

Question 22

Now moving on to the various inflammations that can occur in breast pathology. What is acute mastitis?

Answer 22

Usually when breast feeding – cracks + bacterial infection — red/painful breast + fever

• -Staph: small, localized under nipple (may leave residual indurated scar)
• -Strep: whole breast, marked swelling tenderness (heals w/o scar)

Question 23

What is seen on histology of a patient with Acute Mastitis?

Answer 23

Histology: Necrotic cell debris with neutrophil rich infiltrates

Question 24

What is mammary duct ectasia?

Answer 24

Plasma Cell Mastitis also called Granulomatous Mastitis

• -chronic condition
• -dilated duct ruptures and releases plasma cells and inflammatory cells
• Periareolar mass with thick white nipple secretions
• May lead to nipple retraction and induration which mimics carcinoma

Question 25

What is traumatic fat necrosis?

Answer 25

History of trauma or breast surgery
Large, pendulous breasts
Mimics carcinoma clinically
Fat necrosis, cholesterol clefts, neutrophils, lipid laden macrophages
Later: lymphocytes, fibrosis, cysts +/- calcification

Question 26

Finally what is the bodies reaction to breast implants?

Answer 26

Cosmetic: paraffin or silicone

—Histology: epitheloid cells, foreign body giant cells and macrophages

Question 27

Next topic is fibroadenoma of the breast tissue. What is the etiology ?

Answer 27

Most common benign breast tumor (single, discrete encapsulated nodule 1-10cm)
Women of reproductive age
Etiology= unknown
–estrogen does not cause: only makes bigger
–grow bigger in pregnancy, granuloa theca tumor and polycystic ovarian disease and regress at menopause
–Behaves similar to a leiomyoma
**uterine fibroids not cause by estrogen, but do grow with it .

Question 28

What is the origin and presentation for a patient with a fibroadenoma?

Answer 28

Unilateral
Origin: intralobular stroma
Presentation: found by women on self examination
**Breast mass: mobile, non tender and hard to grasp (defined and well circumscribed)
–“breast mouse”

Question 29

What does the mammogram show for patients with fibroadenoma?

Answer 29

Popcorn calcification

Question 30

Excisional Biopsy is the best test for fibroadenoma, what are the two classifications?

Answer 30

1. Ducts that look like slits: intracanalicular (left)
2. Ducts that look circular or ovoid: pericanalicular (right image)
   - -both types of benign (No clinical relevance of naming)
   - -no chance of malignant transformation

Question 31

Moving on to the next mass in the breast tissue is a Phylloides Tumor (Cystosarcoma phylloides). What is the etiology and origin?

Answer 31

Unilateral in post menopausal women (60-70s)(Note age is a big difference form fibroadenoma)
–origin: intralobular stroma
–etiology: unknown (for sure not estrogen)
Can be benign or malignant
called cystosarcoma phylloides because the origin is stroma of the connective tissue

Question 32

What is the presentation for a patient with Phylloides Tumor?

Answer 32

Post-Menopausal women with unilateral pendulous breast (aka big swinging breast)

Question 33

What is seen on biopsy in patients with phylloides tumor?

Answer 33

Biopsy is the best test:

–Leaflike ducts

Question 34

Phylloides tumor (Cystosacroma Phylloides) can be either benign, borderline or malignant. What are the defining features of each?

Answer 34

Benign: Zonal hypercellularity, mold atypia stromal cells, no stromal overgrowth and mitosis less than 5/HPF
Borderline: Zonal hypercellularity, moderate atypical stromal cells, no stromal overgrowth and mitosis 5-10/HPF
Malignant: More mitosis and hypercellularity of the interlobular stroma (Invasion has now occurred)

Question 35

What are complications of Phylloides Tumor (Cystosarcoma)?

Answer 35

Small chance of benign to malignant

• -most malignant are de novo
• -does not spread through lymph nodes (only breast cancer that does not spread through lymph nodes)
• -Hematogenous spread: liver, lung, brain, bone, kidney

Question 36

Finally the last topic for this card set is Intraductal Papilloma. What is the morphology seen on slide 5?

Answer 36

Lumen contains papilloma
Papilloma lined by inner cuboidal and outer myoepithelial cells
–arrowheads: inner cuboidal facing lumen
–arrows: outer myoepithelial facing the core Core Composed:
CT, Fibroblasts and Blood Vessels

Question 37

What is the etiology and origin of intraductal papilloma?

Answer 37

Etiology: Unknown
Origin: small duct: TDLU
Large duct: lactiferous ducts

Question 38

What are the sites for large duct and small duct papillomas?

Answer 38

Large Duct: solitary situated in lactiferous sinuses of nipple
Small Duct: multiple and located deeper in the ductal system

Question 39

What are the signs and symptoms associated with intraductal papilloma

Answer 39

Seen in Pre-Menopausal Women (35-55)

• –most common cause of blood nipple discharge in women of reproductive age
• –small subareolar tumor a few millimeters in diameter
• -nipple retraction is rare

Question 40

What is the best investigation for a patient with intraductal papilloma?

Answer 40

Excisional Biopsy:

—papilloma into the lumen of the lactiferous ducts if benign layers are normal

Question 41

What are the complications associated with intraductal papilloma?

Answer 41

Multiple intraductal papillomas (intraductal papillomatosis) have an increased chance of being malignant — papillary carcinoma of the breast (Single layer of atypical inner cuboidal cells and no outer myoepithelial) — invasion into the papillary core